Structural analysis of human and macaque mAbs 2909 and 2.5B: implications for the configuration of the quaternary neutralizing epitope of HIV-1 gp120

Structure. 2011 May 11;19(5):691-9. doi: 10.1016/j.str.2011.02.012.

Abstract

The quaternary neutralizing epitope (QNE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and QNE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both mAbs have long beta hairpin CDR H3 regions >20 Å in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for QNE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE Abs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / metabolism
  • Antigens, Viral* / chemistry
  • Antigens, Viral* / immunology
  • Antigens, Viral* / metabolism
  • Crystallography, X-Ray
  • Epitopes / chemistry*
  • Epitopes / immunology
  • HIV Antibodies / chemistry*
  • HIV Antibodies / immunology
  • HIV Antibodies / metabolism
  • HIV Envelope Protein gp120* / chemistry
  • HIV Envelope Protein gp120* / immunology
  • HIV Envelope Protein gp120* / metabolism
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / chemistry*
  • HIV-1 / immunology
  • HIV-1 / metabolism
  • Humans
  • Macaca / immunology*
  • Macaca / metabolism
  • Macaca / virology
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding / immunology
  • Protein Structure, Quaternary

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antigens, Viral
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120

Associated data

  • PDB/3Q6F
  • PDB/3Q6G